Induction of demyelination in the central nervous system （CNS） of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. How- ever, differen...Induction of demyelination in the central nervous system （CNS） of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. How- ever, different mouse strains used result in different pathological outcomes. Moreover, because current medicinal treatments are not always effective in multiple sclerosis patients, so the study of exogenous cell transplantation in an animal model is of great importance. The aims of the present study were to establish an alternative ICR outbred mouse model for studying demyelination and to evaluate the effects of intrave- nous cell transplantation in the present developed mouse model. Two sets of experiments were conducted. Firstly, ICR outbred and BALB/c inbred mice were fed with 0.2% cuprizone for 6 consecutive weeks; then demyelinating scores determined by luxol fast blue stain or immunolabeling with CNPase were evaluated. Secondly, attenuation of demyelination in ICR mice by intravenous injection of mES cells was studied. Scores for demyelination in the brains of ICR mice receiving cell injection （mES cells-injected group） and vehicle （sham-inoculated group） were assessed and compared. The results showed that cuprizone signifi- cantly induced demyelination in the cerebral cortex and corpus callosum of both ICR and BALB/c mice. Additionally, intravenous transplantation of mES cells potentially attenuated demyelination in ICR mice compared with sham-inoculated groups. The present study is among the earliest reports to describe the cuprizone-induced demyelination in ICR outbred mice. Although it remains unclear whether mES cells or trophic effects from mES cells are the cause of enhanced remyelination, the results of the present study may shed some light on exogenous cell therapy in central nervous system demyelinating diseases.展开更多
It is a challenging issue to map Quantitative Trait Loci(QTL)underlying complex discrete traits,which usually show discontinuous distribution;less information,using conventional statistical methods.Bayesian-Markov cha...It is a challenging issue to map Quantitative Trait Loci(QTL)underlying complex discrete traits,which usually show discontinuous distribution;less information,using conventional statistical methods.Bayesian-Markov chain Monte Carlo(Bayesian-MCMC)approach is the key procedure in mapping QTL for complex binary traits,which provides a complete posterior distribution for QTL parameters using all prior information.As a consequence,Bayesian estimates of all interested variables can be obtained straightforwardly basing on their posterior samples simulated by the MCMC algorithm.In our study,utilities of Bayesian-MCMC are demonstrated using simulated several animal outbred full-sib families with different family structures for a complex binary trait underlied by both a QTL;polygene.Under the Identity-by-Descent-Based variance component random model,three samplers basing on MCMC,including Gibbs sampling,Metropolis algorithm;reversible jump MCMC,were implemented to generate the joint posterior distribution of all unknowns so that the QTL parameters were obtained by Bayesian statistical inferring.The results showed that Bayesian-MCMC approach could work well;robust under different family structures;QTL effects.As family size increases;the number of family decreases,the accuracy of the parameter estimates will be improved.When the true QTL has a small effect,using outbred population experiment design with large family size is the optimal mapping strategy.展开更多
基金supported by the Faculty Research Fund,Faculty of Veterinary Medicine,Chiang Mai University,Thailand
文摘Induction of demyelination in the central nervous system （CNS） of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. How- ever, different mouse strains used result in different pathological outcomes. Moreover, because current medicinal treatments are not always effective in multiple sclerosis patients, so the study of exogenous cell transplantation in an animal model is of great importance. The aims of the present study were to establish an alternative ICR outbred mouse model for studying demyelination and to evaluate the effects of intrave- nous cell transplantation in the present developed mouse model. Two sets of experiments were conducted. Firstly, ICR outbred and BALB/c inbred mice were fed with 0.2% cuprizone for 6 consecutive weeks; then demyelinating scores determined by luxol fast blue stain or immunolabeling with CNPase were evaluated. Secondly, attenuation of demyelination in ICR mice by intravenous injection of mES cells was studied. Scores for demyelination in the brains of ICR mice receiving cell injection （mES cells-injected group） and vehicle （sham-inoculated group） were assessed and compared. The results showed that cuprizone signifi- cantly induced demyelination in the cerebral cortex and corpus callosum of both ICR and BALB/c mice. Additionally, intravenous transplantation of mES cells potentially attenuated demyelination in ICR mice compared with sham-inoculated groups. The present study is among the earliest reports to describe the cuprizone-induced demyelination in ICR outbred mice. Although it remains unclear whether mES cells or trophic effects from mES cells are the cause of enhanced remyelination, the results of the present study may shed some light on exogenous cell therapy in central nervous system demyelinating diseases.
基金supported by the National Natural Science Foundation of China(Grant No.30430500).
文摘It is a challenging issue to map Quantitative Trait Loci(QTL)underlying complex discrete traits,which usually show discontinuous distribution;less information,using conventional statistical methods.Bayesian-Markov chain Monte Carlo(Bayesian-MCMC)approach is the key procedure in mapping QTL for complex binary traits,which provides a complete posterior distribution for QTL parameters using all prior information.As a consequence,Bayesian estimates of all interested variables can be obtained straightforwardly basing on their posterior samples simulated by the MCMC algorithm.In our study,utilities of Bayesian-MCMC are demonstrated using simulated several animal outbred full-sib families with different family structures for a complex binary trait underlied by both a QTL;polygene.Under the Identity-by-Descent-Based variance component random model,three samplers basing on MCMC,including Gibbs sampling,Metropolis algorithm;reversible jump MCMC,were implemented to generate the joint posterior distribution of all unknowns so that the QTL parameters were obtained by Bayesian statistical inferring.The results showed that Bayesian-MCMC approach could work well;robust under different family structures;QTL effects.As family size increases;the number of family decreases,the accuracy of the parameter estimates will be improved.When the true QTL has a small effect,using outbred population experiment design with large family size is the optimal mapping strategy.
